Toxicoepigenomics in Lupus

Ray, Donna; Richardson, Bruce C.

doi:10.1002/9781118349045.ch13

Cited by 2 publications

(1 citation statement)

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“…The replication of DNA methylation patterns during mitosis requires S-adenosylmethionine (SAM), the methyl donor, and DNA methyltransferase 1 (Dnmt1), the enzyme that transfers the methyl group from SAM to dC bases in DNA CpG pairs. Therefore, environmental factors such as diet, which provides the methyl donors, and agents that decrease Dnmt1 enzymatic activity may synergize to demethylate DNA in dividing T cells, causing overexpression of the methylation-sensitive immune genes that contribute to lupus flares [14]. T cell Dnmt1 levels are regulated in part by the extracellular receptor kinase (ERK) pathway [15], and we have reported that methylation sensitive T cell genes are overexpressed in transgenic C57BL/6 × SJL mice with an inducible T cell ERK pathway signaling defect.…”

Section: Introductionmentioning

confidence: 99%

Oxidative stress and dietary micronutrient deficiencies contribute to overexpression of epigenetically regulated genes by lupus T cells

Ray¹,

Strickland²,

Richardson³

2018

Clinical Immunology

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Patients with active lupus have altered T cells characterized by low DNA methyltransferase levels. We hypothesized that low DNA methyltransferase levels synergize with low methionine levels to cause greater overexpression of genes normally suppressed by DNA methylation. CD4+ T cells from lupus patients and controls were stimulated with PHA then cultured in custom media with normal or low methionine levels. Oxidative stress was induced by treating the normal CD4+ T cells with peroxynitrite prior to culture. Methylation sensitive gene expression was measured by flow cytometry. Results showed low methionine levels caused greater overexpression of methylation sensitive genes in peroxynitrite treated T cells relative to untreated T cells, and in T cells from lupus patients relative to T cells from healthy controls. In conclusion, low dietary transmethylation micronutrient levels and low DNA methyltransferase levels caused either by oxidative stress or lupus, have additive effects on methylation sensitive T cell gene expression.

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Section: Introductionmentioning

confidence: 99%